Effect of Dapagliflozin on Microvascular Function in Women With Symptoms of Coronary Artery Disease

Myocardial Ischemia Clinical Trial

— SMILE  

Official title:

A Single-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate Microvascular Disease After 12 Weeks of Therapy With Sodium-glucose Co-transporter 2 Inhibitor Compared to Placebo in Symptomatic Women With Non-obstructive Coronary Artery Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05762952
• Other study ID #: HSR220123
• Status: Recruiting
• Phase: Phase 1
• Start date: June 6, 2023
• Est. completion date: March 31, 2025

Study information

• Verified date: April 2024
• Source: University of Virginia
• Contact: Caroline L Flournoy, PhD
• Phone: 4349246104
• Email: clf4w[@]uvahealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to test the effects of a drug (in the drug class called sodium-glucose cotransporter 2 inhibitors) in women who have symptoms of ischemic heart disease. The main questions the study aims to answer are:

Does blood flow in the heart improve with study drug?

Participants will be randomly assigned to a 12-week course of the study drug, dapagliflozin 10mg, or placebo. Blood flow in the heart will be assessed using stress cardiac magnetic resonance imaging at baseline and 12 weeks. The researchers will compare the results from the two groups.

Description:

This single-center clinical investigation is a randomized, double-blind, placebo controlled trial of dapagliflozin in women who have symptoms of myocardial ischemia but in whom obstructive coronary artery disease has been ruled out by testing within 2 years.

Aim: Determine whether dapagliflozin improves coronary blood flow in women.

Participants will be randomly assigned to a 12-week course of dapagliflozin 10mg oral or placebo. Participants will complete study assessments at baseline, 6 weeks of treatment, and 12 weeks of treatment. Peak myocardial blood flows at rest and with pharmacological stress will be assessed using cardiac magnetic resonance imaging at baseline and 12 weeks. Symptom surveys and lab work will be collected at baseline, 6 weeks, and 12 weeks of treatment. Participants will be closely monitored throughout study participation for adverse events. Results will be captured in a database and published in a peer-reviewed journal.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Willing to provide written informed consent.

• Signs and symptoms of suspected ischemia that prompted referral for further evaluation by cardiac catheterization or coronary computed tomography within two years of consent.

• No evidence of obstructive epicardial coronary artery disease (stenosis >50%) of a major epicardial vessel (>3mm) or a fractional flow reserve >0.80 by invasive catheterization or coronary computed tomography. (Participants who have not undergone cardiac catheterization or coronary angiogram within the last 2 years for their clinical care will be screened with computed angiogram of the coronary arteries to confirm eligibility).

• Estimated glomerular filtration rate =30ml/min/1.73m2 at enrollment

• For subjects having a history of type 2 diabetes mellitus: approval of diabetes care/prescribing provider

Exclusion Criteria:

• History of non-ischemic cardiomyopathy with left ventricular ejection fraction <40% or hypertrophic cardiomyopathy.

• History of congestive heart failure, severe pulmonary disease, liver disease

• History of Acute coronary syndrome within previous 30 days

• Stroke within the last 180 days or intracranial hemorrhage at any time.

• Severe Valvular disease

• Life expectancy <3 years, due to non-cardiovascular comorbidity.

• Pregnancy or women who are breast-feeding

• Type 1 diabetes mellitus

• History of diabetic ketoacidosis in subjects with Type 2 Diabetes Mellitus

• Symptomatic hypotension or systolic blood pressure <95 mmHg on 2 consecutive measurements

• Active malignancy requiring treatment at the time of visit

• Severe, unstable, or rapidly progressing renal disease at the time of randomization

• History of recurrent urinary tract, bladder, or kidney infections

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Dapagliflozin 10mg Tab
Once daily oral dapagliflozin 10mg
• Placebo
Placebo capsules formulated by pharmacy to be indistinguishable from active drug

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in myocardial perfusion reserve	Myocardial microvascular perfusion, defined as myocardial perfusion reserve as assessed by stress cardiac magnetic resonance imaging	Baseline and after 12 weeks of treatment